A controlled depolymerization of some natural GAGs, as heparin, heparan sulphate (HS), dermatansulphate (DS) is an attractive but, in practice, difficult task.
Interest arises from some experimental observations, according to which bioavailability and biological effects for some GAGs, when orally or parenterally administered in experimental models or in humans, are dependent on the mean molecular weight (MW). As an example, commercial heparin is a well known anticlotting agent, due to its activating properties, as a co-factor, on a powerful protease inhibitor, anti-thrombin III (At-III). Heparin is a sulphated GAG, with NW=12.000 D, corresponding to about 20 disaccharide units and in hemocoagulation it inhibits 5 factors, namely F XII, F XI, FIX, F X, FII. Recently, it was discovered that heparin fractions having NW=4.000-6.000 D (low molecular weight heparins, LMWH), affect inhibition on some factors but not on others, and peculiarly on some key factors in venous thrombosis onset, such as F X. Consequently, LMWH could be considered as effective anti-thrombotic agents with less risk of hemorraghe than commercial heparin.
It has also been found that the half-life in bloodstream for LMWH is longer than for normal heparin. Therefore, a long term therapy can be established, avoiding drip infusions and rebound phenomena.
A further advantage for LMWH is the absence of interference in platelet agregation, an undesirable effect which in the past, caused severe thrombocytopenia in some patients during heparin administration.